The objectives of these investigations are to extend and expand experimental studies on the effects of heavy metals upon mammalian embryonic development. This laboratory has identified a number of heavy metals which have specific teratogenic effects on the mammalian embryo. These metals are: lead, cadmium, arsenic, mercury and indium. We plan to investigate further the effects of these metals by four different but complementary experimental approaches. First, continuing studies on the synergism, antagonism and interaction of various combinations of heavy metals and their effects on embryonic differentiation will be conducted. Second, the localization of these heavy metals in placental and embryonic tissues as well as routes and rates of placental permeability will be studied by use of radioisotopes (gamma counting, radioautography) and by direct measurement of metal concentrations (anodic stripping voltametry). These studies will be directed toward a further definition of the ontogency of the specific malformation induced by each metal. Third, we shall follow interesting new leads on the genetic susceptibility of reproductive tissues to specific heavy metals and attempt to expand these observations to embryonic differentiation by use of teratogenic models in inbred strains of mice and hamsters. Finally, we shall pay particular attention to the effects of lead on reproductive tissues in an attempt to determine the effects of this metal on gametogenic tissue, its route of transmission through the placenta, and the effects of low levels of lead on several parameters of pregnancy.